The roles of long non-coding RNAs in Alzheimer's disease diagnosis, treatment, and their involvement in Alzheimer's disease immune responses.

Alzheimer's disease (AD) is the most frequent type of dementia, presenting a substantial danger to the health and well-being of the aged population. It has arisen as a significant public health problem with considerable socioeconomic repercussions. Unfortunately, no effective treatments or diagnostic tools are available for Alzheimer's disease. Despite substantial studies on the pathophysiology of Alzheimer's, the molecular pathways underpinning its development remain poorly understood. Long non-coding RNAs (lncRNAs) vary in size from 200 nucleotides to over 100 kilobytes and have been found to play critical roles in various vital biological processes that play critical in developing Alzheimer's disease. This review intends to examine the functions of long non-coding RNAs in diagnosing and treating Alzheimer's disease and their participation in immunological responses associated with AD.

Nobiletin alleviates cisplatin-induced ototoxicity via activating autophagy and inhibiting NRF2/GPX4-mediated ferroptosis.

Nobiletin, a citrus polymethoxy flavonoid with antiapoptotic and antioxidative properties, could safeguard against cisplatin-induced nephrotoxicity and neurotoxicity. Cisplatin, as the pioneer of anti-cancer drug, the severe ototoxicity limits its clinical applications, while the effect of nobiletin on cisplatin-induced ototoxicity has not been identified. The current study investigated the alleviating effect of nobiletin on cisplatin-induced ototoxicity and the underlying mechanisms. Apoptosis and ROS formation were evaluated using the CCK-8 assay, Western blotting, and immunofluorescence, indicating that nobiletin attenuated cisplatin-induced apoptosis and oxidative stress. LC3B and SQSTM1/p62 were determined by Western blotting, qPCR, and immunofluorescence, indicating that nobiletin significantly activated autophagy. Nobiletin promoted the nuclear translocation of NRF2 and the transcription of its target genes, including Hmox1, Nqo1, and ferroptosis markers (Gpx4, Slc7a11, Fth, and Ftl), thereby inhibiting ferroptosis. Furthermore, RNA sequencing analysis verified that autophagy, ferroptosis, and the NRF2 signaling pathway served as crucial points for the protection of nobiletin against ototoxicity caused by cisplatin. Collectively, these results indicated, for the first time, that nobiletin alleviated cisplatin-elicited ototoxicity through suppressing apoptosis and oxidative stress, which were attributed to the activation of autophagy and the inhibition of NRF2/GPX4-mediated ferroptosis. Our study suggested that nobiletin could be a prospective agent for preventing cisplatin-induced hearing loss.

4-octyl itaconate alleviates cisplatin-induced ferroptosis possibly via activating the NRF2/HO-1 signalling pathway.

Ferroptosis, characterized by iron-dependent lipid reactive oxygen species (ROS) accumulation, plays a pivotal role in cisplatin-induced ototoxicity. Existing research has suggested that in cisplatin-mediated damage to auditory cells and hearing loss, ferroptosis is partially implicated. 4-Octyl itaconate (4-OI), derived from itaconic acid, effectively permeates cell membranes, showcasing potent anti-inflammatory as well as antioxidant effects in several disease models. Our study aimed to investigate the effect of 4-OI on cisplatin-induced ferroptosis and the underlying molecular mechanisms. The survival rates of HEI-OC1 cells and mice cochlea hair cells were measured by CCK8 and immunofluorescence, respectively. The auditory brainstem response (ABR) audiometry was used to detect changes in hearing thresholds in mice before and after treatment. Levels of ROS were evaluated by DCFH-DA. Real-time PCR quantified inflammatory cytokines TNF-α, IL-6 and IL-1ß. Network Pharmacology and RNA sequencing (RNA-seq) analysis of the potential mechanism of 4-OI resistance to cisplatin-induced ferroptosis. The expressions of ferroptosis-related factors (GPX4, SLC7A11 and PTGS2) and important antioxidant factors (NRF2, HO-1, GCLC and NQO1) were tested by real-time PCR, Western blot and immunofluorescence. Results demonstrated cisplatin-induced significant ROS and inflammatory factor release, reduced NRF2 expression, hindered nuclear translocation and activated ferroptosis. Pretreatment with 4-OI exhibited anti-inflammatory and antioxidant effects, along with resistance to ferroptosis, ultimately mitigating cisplatin-induced cell loss. In the present study, we show that 4-OI inhibits cisplatin-induced ferroptosis possibly through activation of the NRF2/HO-1 signalling pathway, thereby exerting a protective effect against cisplatin-induced damage to auditory cells, and providing a new therapeutic strategy for cisplatin-induced hearing loss.

Provenance and family variations in early growth of Manchurian walnut (Juglans mandshurica Maxim.) and selection of superior families.

This study, conducted in China in November 2020, was aimed at exploring the variations in growth traits among different provenances and families as well as to select elite materials of Juglans mandshurica. Thus, seeds of 44 families from six J. mandshurica provenances in Heilongjiang and Jilin provinces were sown in the nursery and then transplanted out in the field. At the age of 5 years, seven growth traits were assessed, and a comprehensive analysis was conducted as well as selection of provenance and families. Analysis of variance revealed statistically significant (P < 0.01) differences in seven growth traits among different provenances and families, thereby justifying the pursuit of further breeding endeavors. The genetic coefficient of variation (GCV) for all traits ranged from 5.44% (branch angle) to 21.95% (tree height) whereas the phenotypic coefficient of variation (PCV) ranged from 13.74% (tapering) to 38.50% (branch number per node), indicating considerable variability across the traits. Further, all the studied traits except stem straightness degree, branch angle and branch number per node, showed high heritability (Tree height, ground diameter, mean crown width and tapering, over 0.7±0.073), indicating that the variation in these traits is primarily driven by genetic factors. Correlation analysis revealed a strong positive correlation (r > 0.8) between tree height and ground diameter (r = 0.86), tree height and mean crown width (r = 0.82), and ground diameter and mean crown width (r = 0.83). This suggests that these relationships can be employed for more precise predictions of the growth and morphological characteristics of trees, as well as the selection of superior materials. There was a strong correlation between temperature factors and growth traits. Based on the comprehensive scores in this study, Sanchazi was selected as elite provenance. Using the top-percentile selection criteria, SC1, SC8, DJC15, and DQ18 were selected as elite families. These selected families exhibit genetic gains of over 10% in tree height, ground diameter and mean crown width, signifying their significant potential in forestry for enhancing timber production and reducing production cycles, thereby contributing to sustainable forest management. In this study, the growth traits of J. mandshurica were found to exhibit stable variation, and there were correlations between these traits. The selected elite provenance and families of J. mandshurica showed faster growth, which is advantageous for the subsequent breeding and promotion of improved J. mandshurica varieties.

Inhibition of Alzheimer's disease by 4-octyl itaconate revealed by RNA-seq transcriptome analysis.

AIMS: This study aimed to examine the therapeutic effects and response mechanisms of 4-OI in Alzheimer's disease (AD). METHODS: In this study, network pharmacology was employed to analyze potential targets for AD drug therapy. Immunofluorescence and quantitative reverse transcription polymerase chain reaction (qRT-PCR) techniques were utilized to detect inflammatory phenotypes in a 4-OI-resistant mouse microglia cell line (BV2). We conducted four classical behavioral experiments, namely the open field test, new object recognition test, Y maze test, and Morris water maze, to assess the emotional state and cognitive level of APPswe/PS1dE9 (referred to as APP/PS1) mice after 4-OI treatment. Hematoxylin and eosin (HE) staining, along with immunofluorescence staining, were performed to detect amyloid (Aß) deposition in mouse brain tissue. To explore the potential molecular mechanisms regulating the effects of 4-OI treatment, we performed RNA-SEQ and transcription factor prediction analyses. Additionally, mouse BV2 cells underwent Western blotting analysis to elucidate potential molecular mechanisms underlying the observed effects. RESULTS: We discovered that 4-OI exerts an inhibitory effect on neuroinflammation by promoting autophagy. This effect is attributed to the activation of the AMPK/mTOR/ULK1 pathway, achieved through enhanced phosphorylation of AMPK and ULK1, coupled with a reduction in mTOR phosphorylation. Furthermore, 4-OI significantly enhances neuronal recovery in the hippocampus and diminishes Aß plaque deposition in APP/PS1 mice, improved anxiety in mice, and ultimately led to improved cognitive function. CONCLUSIONS: Overall, the results of this study demonstrated that 4-OI improved cognitive deficits in AD mice, confirming the therapeutic effect of 4-OI on AD.

Subtrochanteric Osteotomy in Direct Anterior Approach Total Hip Arthroplasty for Crowe IV Dysplasia-Surgical Technique and Literature Review.

For Crowe IV dysplasia, the clinical efficacy and surgical technique of subtrochanteric osteotomy (SO) within the direct anterior approach total hip arthroplasty (DAA-THA) was a subject of debate. This study aimed to describe the surgical technique and clinical outcomes in 11 cases of SO in DAA-THA and to summarize the relevant literature on this topic. Between June 2016 and June 2023, we retrospectively evaluated patients diagnosed with Crowe IV hip dysplasia at our institution. Criteria identified 11 patients who underwent SO during DAA-THA. Comprehensive data encompassing demographic information, radiological data, prosthetic implant type, and surgical intricacies were collected. In addition, an exhaustive review of existing case series literature was undertaken utilizing the PubMed databases. There were no revisions, deaths, dislocations, or infections. One hip (9.09%) had an intraoperative proximal split fracture, two hips (18.2%) had lower limb deep vein thrombosis, and one hip (9.09%) had symptoms of femoral nerve injury. Radiological data showed improved bilateral femoral offset, leg length discrepancy, and anatomical acetabular. During the mean follow-up of 2.18(1.06-2.46) years, patients demonstrated enhanced functional outcomes, with average changes of 25.2 in the Harris hip score and 47 in the WOMAC score. Reviewing the literature, most studies have favored S-ROM prostheses and transverse osteotomy techniques. Intraoperative fractures were notably frequent, with rates peaking at 25%. Nonunion and nerve injury were secondary common complications. SO via DAA-THA may offer satisfactory clinical and radiographic outcomes, but the literature review underscores the need for heightened awareness of intraoperative fracture risk. Proximal detachment of the vastus intermedius plays a pivotal role in SO exposure through the DAA.

Attenuated memory impairment and neuroinflammation in Alzheimer's disease by aucubin via the inhibition of ERK-FOS axis.

Alzheimer's disease (AD) is a degenerative illness accompanied by cognitive and memory loss. In addition to the widely accepted, convincing amyloid cascade hypothesis, the activation of glial cells and neuroinflammation, especially the microglia-mediated neuroinflammation, has an essential role in the development and progression of AD. Therefore, the anti-inflammatory treatment is becoming a promising therapeutic strategy. Aucubin (Au) is a natural product derived from many plants with anti-inflammatory and antioxidant activities. Up to now, no research has been conducted to investigate the anti-inflammatory effects of Au and its neuroprotective quality on AD and the potential molecular mechanisms of its medical roles. In our study, the results of network pharmacology revealed the potential therapeutic effect of Au on AD. The results of studies in vivo showed that Au improved the behaviors, counteracted cognitive and memory deficits, and ameliorated AD-like pathological features of the mouse brain, e.g., the deposition of Aß plaques, neuronal damage, and inflammatory responses induced by glial cell overactivation, in APP/PS1 mice. The transcriptome sequencing further confirmed that the pathological symptoms of AD could be reversed by inhibiting the ERK/FOS axis to alleviate the inflammatory response. The in vitro experiments revealed that Au suppressed the BV2 cell activation, inhibited the phosphorylation of ERK1/2 and the expression of c-FOS, and reduced the LPS-induced inflammatory mediator production by BV2 cells and primary astrocytes. Our study suggested that Au exerted its neuroprotective effects by inhibiting the inflammatory responses, which could be a promising treatment of AD.

Palladium-Catalyzed Synthesis of Indanone via C-H Annulation Reaction of Aldehydes with Norbornenes.

A novel methodology for the synthesis of indanone derivates has been developed. The palladium-catalyzed annulation reaction of o-bromobenzaldehydes with norbornene derivatives is achieved through extremely concise reaction processes. The indanone skeleton was established directly via C-H activation of the aldehyde group under a mild reaction condition. This method is simple and practical, which simplified the traditional synthesis method for the rapid construction of indanone.

Variations in the oral microbiome and metabolome of methamphetamine users.

Drug addiction can seriously damage human physical and mental health, while detoxification is a long and difficult process. Although studies have reported changes in the oral microbiome of methamphetamine (METH) users, the role that the microbiome plays in the process of drug addiction is still unknown. This study aims to explore the function of the microbiome based on analysis of the variations in the oral microbiome and metabolome of METH users. We performed the 16S rRNA sequencing analysis based on the oral saliva samples collected from 278 METH users and 105 healthy controls (CTL). In addition, the untargeted metabolomic profiling was conducted based on 220 samples. Compared to the CTL group, alpha diversity was reduced in the group of METH users and the relative abundances of Peptostreptococcus and Gemella were significantly increased, while the relative abundances of Campylobacter and Aggregatibacter were significantly decreased. Variations were also detected in oral metabolic pathways, including enhanced tryptophan metabolism, lysine biosynthesis, purine metabolism, and steroid biosynthesis. Conversely, the metabolic pathways of porphyrin metabolism, glutathione metabolism, and pentose phosphate were significantly reduced. It was speculated that four key microbial taxa, i.e., Peptostreptococcus, Gemella, Campylobacter, and Aggregatibacter, could be involved in the toxicity and addiction mechanisms of METH by affecting the above metabolic pathways. It was found that with the increase of drug use years, the content of tryptamine associated with neuropsychiatric disorders was gradually increased. Our study provides novel insights into exploring the toxic damage and addiction mechanisms underlying the METH addiction.IMPORTANCEIt was found that with the increase of drug use years, the content of tryptamine associated with neuropsychiatric disorders gradually increased. The prediction models based on oral microbiome and metabolome could effectively predict the methamphetamine (METH) smoking. Our study provides novel insights into the exploration of the molecular mechanisms regulating the toxic damage and addiction of METH as well as new ideas for early prevention and treatment strategies of METH addiction.

Effectiveness of Group-Based Interventions for Fall Prevention Among Community-Dwelling Older Adults - 7 Regions, 6 PLADs, China, 2019-2020.

What is already known about this topic?: Many of the current studies focusing on fall prevention interventions have been conducted in hospital settings within a select few urban areas in China, thus yielding limited evidence on the effectiveness of large-scale, multicenter, community-based interventions. What is added by this report?: In comparison to the control group, participants in the intervention group exhibited a 64% reduction in fall risk. Group-based fall prevention programs have demonstrated efficacy in mitigating fall risk among the elderly population. What are the implications for public health practice?: Group-based fall prevention interventions serve as a significant adjunctive resource for the management of elderly health within communities and offer compelling evidence to support the incorporation of fall prevention strategies into health policy frameworks in China.

Omaveloxolone ameliorates cognitive dysfunction in APP/PS1 mice by stabilizing the STAT3 pathway.

AIMS: To determine the availability and the potential molecular mechanisms underlying the therapeutic effect of omaveloxolone (RTA408) on Alzheimer's Disease (AD). MATERIALS AND METHODS: This study employed network pharmacology to assess the feasibility of drug treatment of AD. To determine the cognitive status and emotional state of APPswe/PS1dE9 (APP/PS1) mice after the RTA408 treatment, three classical behavioral experiments (water maze, Y-maze, and open field test) were conducted. Immunofluorescence and immunohistochemical staining were utilized to evaluate hippocampal neuronal status and amyloid (Aß) deposition in mice. RNA-seq and transcription factor prediction analyses were performed to explore the potential molecular mechanisms regulating the therapeutic effects of RTA408. Molecular docking was employed to predict the direct drug targets. To validate these molecular mechanisms, quantitative reverse transcription PCR (qRT-PCR), Western blotting, and immunofluorescence analyses were performed in two instrumental cell lines, i.e., mouse hippocampal neuronal cells (HT22) and microglia (BV2). RESULTS: RTA408 was revealed with the capability to reduce Aß plaque deposition and to restore damaged neurons in the hippocampal region of APP/PS1 mice, ultimately leading to an improvement in cognitive function. This beneficial effect was achieved by balancing the STAT3 pathway. Specifically, RTA408 facilitated the activations of both STAT3/OXR1 and NRF2/ARE axes, thereby enhancing the compromised resistance in neurons to oxidative stress. RTA408 inhibited the NFκB/IL6/STAT3 pathway, effectively countering the neuroinflammation triggered by microglial activation. CONCLUSION: RTA408 is revealed with promising potential in the treatment of AD based on preclinical data.

Implications of LDH in patients with coronavirus disease 2019 pneumonia.

Objective: The objective of this study was to explore the value of serum lactic dehydrogenase (LDH) in the early diagnosis and prognostic evaluation of pneumonia associated with the novel coronavirus infection. Methods: A total of 101 patients with coronavirus disease 2019 (COVID-19) pneumonia were included in the study. According to the severity of the initial chest computed tomography (CT), the patients were divided into the ordinary pneumonia group and the severe pneumonia group and then divided into the remission group and the nonremission group according to the changes of the chest CT after medication treatment. The differences in general characteristics, underlying diseases, clinical symptoms, laboratory findings, and imaging examination outcomes between groups were observed retrospectively. To analyze the diagnostic performance of LDH, receiver operating characteristic (ROC) curves were constructed and the area under the curve (AUC) was calculated. Results: Compared with ordinary pneumonia patients, patients in the severe group presented with significantly higher LDH, neutrophil count, high-sensitivity troponin T (HS-TnT), C-reactive protein (CRP), human serum amyloid A (SAA), N-terminal pro-brain natriuretic peptide (NTproBNP), and D-dimer. Compared with remission patients, non-remission patients presented with significantly higher LDH, neutrophil count, HS-TnT, CRP, SAA, procalcitonin (PCT), creatine kinase-MB mass (CKMB_M), NTproBNP, and D-dimer. In multivariate logistic regression analysis, we found that LDH [odds ratio (OR), 1.015; 95% confidence interval (CI), 1.006-1024; p = 0.001] and neutrophil count (OR, 1.352; 95% CI, 1.008-1.811; p = 0.044) were independently associated with exacerbation in COVID-19 patients. For ROC analysis, the AUC was 0.833 (95% CI, 0.729-0.936; p < 0.001) when we use the LDH value of 256.69 U/L to discriminate the ordinary pneumonia and severe pneumonia patients. The AUC was 0.759 (95% CI, 0.603-0.914; p = 0.008) and the sensitivity is 92.3% when we combined the LDH (cutoff value 258.46 U/L) and the neutrophil count (cutoff value 6.76 × 109/L) to discriminate remission and non-remission patients. Conclusion: The level of LDH is associated with the severity of COVID-19 pneumonia and can be used as important indicators to evaluate the prognosis of patients.

Helicobacter pylori intragastric colonization and migration: Endoscopic manifestations and potential mechanisms.

After being ingested and entering the human stomach, Helicobacter pylori (H. pylori) adopts several effective strategies to adhere to and colonize the gastric mucosa and move to different regions of the stomach to obtain more nutrients and escape from the harsher environments of the stomach, leading to acute infection and chronic gastritis, which is the basis of malignant gastric tumors. The endoscopic manifestations and pathological features of H. pylori infection are diverse and vary with the duration of infection. In this review, we describe the endoscopic manifestations of each stage of H. pylori gastritis and then reveal the potential mechanisms of bacterial intragastric colonization and migration from the perspective of endoscopists to provide direction for future research on the effective therapy and management of H. pylori infection.

The compared study about femoral stem malalignment with or without the special curved rasp during DAA total hip arthroplasty.

OBJECTIVE: To investigate whether the application of a curved rasp on the femoral side is effective in reducing the incidence of stem malalignment in total hip replacement with direct anterior approach (DAA-THA), followed by the analysis of the independent risk factors affecting stem malalignment. METHODS: Retrospective analysis was carried out covering 160 patients undergoing DAA-THA from January 2019 to December 2021, with Tri-Lock (BPS, Depuy) stem applied in all 113 patients were screened according to inclusion and exclusion criteria. The data of gender, age, body mass index, preoperative diagnoses, Dorr classification, FAR ratio, pelvic morphology ratio, WOMAC scores, were analyzed to explore the independent factors influencing the malalignment of the femoral prosthesis implantation. Then data of patients were divided into group A and group B according to whether the curved rasp was taken during the operation. The chi-square test was performed to compare the incidence of femoral stem malalignment between the two groups. RESULTS: There revealed two independent risk factors: BMI and FAR ratio that affected femoral stem malalignment. The increased BMI was associated with a higher probability of femoral stem malalignment (P<0.05), the probability of malalignment of femoral stem in FAR ratio<1 was 1.15 times higher than that in FAR>1(OR = 1.15, 95% CI: 1.03-1.28, P<0.05). Further grouping analysis showed that the incidence of femoral stem malalignment in patients with intraoperative application of curved rasp was 27%, while in patients without curved rasp, the incidence of femoral stem malalignment increased significantly to 48.7%(P<0.05). The placement angle of prosthesis in group A was significantly better than that in group B, especially mild femoral stem malalignment (0%) and severe femoral stem malalignment (2.70%), and the difference was statistically significant (P < 0.05). There found no significant difference in age, gander, intraoperative complications and last follow-up assessment of WOMAC scores between the two groups of patients. CONCLUSIONS: In DAA-THA, BMI and FAR ratio act as the independent risk factors for femoral stem malalignment. Intraoperative use of a curved rasp significantly reduces the incidence of malalignment of the femoral stem.

The effects of microglia-associated neuroinflammation on Alzheimer's disease.

Alzheimer's disease (AD) is defined as a severe chronic degenerative neurological disease in human. The pathogenic mechanism of AD has been convincingly elucidated by the "amyloid cascade hypothesis" with the main focus of the pathological accretion of ß-amyloid (Aß) peptides outside the cell. However, increasing evidence suggests that this hypothesis is weak in explaining the pathogenesis of AD. Neuroinflammation is crucial in the development of AD, which is proven by the elevated levels of inflammatory markers and the identification of AD risk genes relevant to the innate immune function. Here, we summarize the effects of microglia-mediated neuroinflammation on AD, focusing on the temporal and spatial changes in microglial phenotype, the interactions among microglia, Aß, tau, and neurons, and the prospects and recent advances in neuroinflammation as a diagnostic and therapeutic target of AD.

Differential expression of pyroptosis-related genes in the hippocampus of patients with Alzheimer's disease.

BACKGROUND: Alzheimer's disease (AD) is a progressive, neurodegenerative disorder with insidious onset. Some scholars believe that there is a close relationship between pyroptosis and AD. However, studies with evidence supporting this relationship are lacking. MATERIALS AND METHODS: The microarray data of AD were retrieved from the Gene Expression Omnibus (GEO) database with the datasets merged using the R package inSilicoMerging. R software package Limma was used to perform the differential expression analysis to identify the differentially expressed genes (DEGs). We further performed the enrichment analyses of the DEGs based on Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) databases to identify the metabolic pathways with a significant difference. The Gene Set Enrichment Analysis (GSEA) was applied to identify the significant pathways. The protein-protein interaction (PPI) network was constructed based on the STRING database with the hub genes identified. Quantitative real-time PCR (qRT-PCR) analyses based on HT22 cells were performed to validate the findings based on the microarray analysis. Gene expression correlation heatmaps were generated to evaluate the relationships among the genes. RESULTS: A new dataset was derived by merging 4 microarray datasets in the hippocampus of AD patients in the GEO database. Differential gene expression analysis yielded a volcano plot of a total of 20 DEGs (14 up-regulated and 6 down-regulated). GO analysis revealed a group of GO terms with a significant difference, e.g., cytoplasmic vesicle membrane, vesicle membrane, and monocyte chemotaxis. KEGG analysis detected the metabolic pathways with a significant difference, e.g., Rheumatoid arthritis and Fluid shear stress and atherosclerosis. The results of the Gene Set Enrichment Analysis of the microarray data showed that gene set ALZHEIMER_DISEASE and the gene set PYROPTOSIS were both up-regulated. PPI network showed that pyroptosis-related genes were divided into two groups. In the Aß-induced HT22 cell model, three genes (i.e., BAX, IL18, and CYCS) were revealed with significant differences. Gene expression correlation heatmaps revealed strong correlations between pyroptotic genes and AD-related genes. CONCLUSION: The pyroptosis-related genes BAX, IL18, and CYCS were significantly different between AD patients and normal controls.

Identification of a novel AIFM1 variant from a Chinese family with auditory neuropathy.

Background: Auditory neuropathy (AN) is a specific type of hearing loss characterized by impaired language comprehension. Apoptosis inducing factor mitochondrion associated 1 (AIFM1) is the most common gene associated with late-onset AN. In this study, we aimed to screen the pathogenic variant of AIFM1 in a Chinese family with AN and to explore the molecular mechanism underlying the function of such variant in the development of AN. Methods: One patient with AN and eight unaffected individuals from a Chinese family were enrolled in this study. A comprehensive clinical evaluation was performed on all participants. A targeted next-generation sequencing (NGS) analysis of a total of 406 known deafness genes was performed to screen the potential pathogenic variants in the proband. Sanger sequencing was used to confirm the variants identified in all participants. The pathogenicity of variant was predicted by bioinformatics analysis. Immunofluorescence and Western blot analyses were performed to evaluate the subcellular distribution and expression of the wild type (WT) and mutant AIFM1 proteins. Cell apoptosis was evaluated based on the TUNEL analyses. Results: Based on the clinical evaluations, the proband in this family was diagnosed with AN. The results of NGS and Sanger sequencing showed that a novel missense mutation of AIFM1, i.e., c.1367A > G (p. D456G), was identified in this family. Bioinformatics analysis indicated that this variant was pathogenic. Functional analysis showed that in comparison with the WT, the mutation c.1367A > G of AIFM1 showed no effect on its subcellular localization and the ability to induce apoptosis, but changed its protein expression level. Conclusion: A novel variant of AIFM1 was identified for the first time, which was probably the genetic cause of AN in a Chinese family with AN.

Direct anterior versus posteriorlateral approachs for clinical outcomes after total hip arthroplasty in the treatment of severe DDH.

BACKGROUND: The total hip arthroplasty (THA) has gained popularity in in the treatment of severe developmental dysplasia of the hip (DDH). the posterior lateral approach (PLA) has good clinical efficacy and has been confirmed by the majority clinicians. Nevertheless, controversy exists regarding longer-term benefits of the direct anterior approach (DAA). The objective of this study was to investigate the clinical efficacy and placement of S-ROM prosthesis in the treatment of severe DDH by The total hip arthroplasty (THA) with different surgical approaches. METHODS: A retrospective analysis was performed on 42 patients with severe DDH admitted to our hospital from August 2015 to February 2022, who were treated with S-ROM prosthesis for total hip arthroplasty and subtrochanteric osteotomy of the femur. They were divided into DAA group and PLA group according to different surgical approaches. Perioperative indicators and imaging data were collected. RESULTS: The surgery time, intraoperative blood loss, and creatine kinase difference in DAA group and PLA group was without a statistically significant difference (P > 0.05). The postoperative length of hospitalization was shorter in the DAA group than in the PLA group (6.50 ± 3.15 vs 9.18 ± 4.93, P = 0.045). The acetabular abduction angles、the acetabular anteversion angles, the safe area ratio, The difference of femoral eccentricity, and the vertical difference of rotation center in DAA group and PLA group, there was no statistical significance (P > 0.05). Statistically significant differences were detected the horizontal difference of rotation center (P = 0.044). CONCLUSIONS: Total hip arthroplasty with S-ROM prosthesis is a feasible procedure for severe dysplastic DDH. The clinical efficacy and prosthesis placement parameters of DAA approach are advantage to those of PLA approach.